Ancora 2013.
| Study characteristics | ||
| Methods | Multi‐centre randomised double‐blind placebo‐controlled study | |
| Participants | 131 preterm infants (22 to 32 weeks) mechanically ventilated during the first 72 hours of life were eligible for inclusion Exclusion criteria: known genetic or chromosomal disorders; severe IVH (grade III and intraparenchymal haemorrhage); cystic PVL; need for postoperative analgesic therapy during the first week of life; participation in another clinical trial; probable rapid extubation | |
| Interventions | Fentanyl group (n = 64): intravenous loading dose of 1 microg/kg in 30 minutes, followed by continuous intravenous infusion of 1 mg/kg/hour Placebo group (n = 67): continuous infusion of placebo Masked treatment was started within 24 hours from initiation of MV and had to be continued until the end of MV (if interrupted before 7 days of life). After the seventh day of life, newborns still receiving MV were treated for pain according to local protocols. Infants could receive open‐label boluses of fentanyl as required In both groups, infants could receive open‐label boluses of fentanyl as required | |
| Outcomes | Primary outcome: acute pain response to daily heel prick (assessed by PIPP Scale); prolonged pain measured 3 times daily on the EDIN validated algometric scale Secondary outcomes: infant’s clinical status; duration of hospitalisation; duration of MV; chronic lung disease (need for supplemental oxygen at 36 weeks' PMA); use of MV at 1 week of age; duration of the first cycle of MV (hours); age at full enteral feeding (i.e. milk volume of 150 mL/kg/d); age at first meconium passage (hours); IVH, cystic PVL, or death within 28 days of life; chest wall rigidity; bladder size during first week of life. Diuresis, blood pressure, and use of vasopressors were recorded as well At 24 months' corrected age, developmental assessment was performed with the revised Griffiths Mental Development Scales, providing a general developmental quotient (DQ) of infants’ abilities and 5 subscale quotients (locomotor, personal and social, hearing and language, eye and hand co‐ordination, performance) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | The randomisation code was developed with a computerised random number generator |
| Allocation concealment (selection bias) | Low risk | Allocation was made by a request sent to the local pharmacy, which had a specific randomisation list, stratified by GA and balanced in blocks of 6 at 1:1, developed by the pharmacy at the co‐ordinating centre |
| Blinding of participants and personnel (performance bias) | Low risk | The local pharmacy prepared study medication (fentanyl or placebo) and packed it in a similar way |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "double‐blind design" |
| Incomplete outcome data (attrition bias) | Low risk | All infants accounted for For follow‐up study (Ancora 2017), outcomes were missing for more than 10% of participants, although dropout did not differ between treatment groups (23.5% and 25.0% lost at follow‐up in fentanyl and placebo groups, respectively) |
| Selective reporting (reporting bias) | Low risk | All outcomes reported |
| Other bias | Low risk | Study appears to be free of other sources of bias |